The growing application backlog and median time for ANDA approval by FDA’s Office of Generic Drugs (“OGD”) has been a thorn in the side of the generic drug industry for quite some time now. As we previously reported, the ANDA backlog earlier this year was poised to top 2,000 applications and the median ANDA approval time in Fiscal Year 2009 was 26.70 months. This is up from 21.65 months in Fiscal Year 2008 and up from 17.3 months in Fiscal Year 2003, shortly after which the Medicare Modernization Act (“MMA”) was enacted. Today, the ANDA backlog has surpassed the 2,000 application mark and is reportedly growing at about 100 applications per month; and we understand that the median ANDA approval time is edging closer to 30 months from application submission.

Although a median approval time that hits or exceeds 30 months is concerning in and of itself, it is especially concerning for those companies that are “first applicants” who qualify for 180-day exclusivity for a particular drug product. One of the six 180-day exclusivity provisions added to the FDC Act by Title XI of the MMA – i.e., FDC Act § 505(j)(5)(D)(i)(IV) – “Failure to obtain tentative approval” – provides that 180-day exclusivity eligibility is forfeited if:

The first applicant fails to obtain tentative approval of the application within 30 months after the date on which the application is filed, unless the failure is caused by a change in or a review of the requirements for approval of the application imposed after the date on which the application is filed.

The 2007 FDA Amendments Act clarified FDC Act § 505(j)(5)(D)(i)(IV), such that if “approval of the [ANDA] was delayed because of a [citizen] petition, the 30-month period under such subsection is deemed to be extended by a period of time equal to the period beginning on the date on which the Secretary received the petition and ending on the date of final agency action on the petition (inclusive of such beginning and ending dates) . . . .” (FDC Act § 505(q)(1)(G)). FDA explained in the Agency’s Acarbose Exclusivity Letter Decision that the reference to “approval” in FDC Act FDC Act § 505(q)(1)(G) means that “section 505(j)(5)(D)(i)(IV) also applies when the first applicant is eligible for a final approval, but not for a tentative approval. The absence of patent or exclusivity protection that would necessitate a tentative – rather than final – approval, does not exempt a first applicant from the requirement that it show that its application meets the scientific and technical requirements of 505(j) within 30 months of filing.”

Although FDC Act § 505(j)(5)(D)(i)(IV) includes an exception where the failure to obtain timely approval will not result in a forfeiture of 180-day exclusivity eligibility if “the failure is caused by a change in or a review of the requirements for approval of the application imposed after the date on which the application is filed,” FDA believes this is the only circumstance supported by the statute. As FDA explained in the Agency’s Dorzolamide-Timolol Maleate Ophthalmic Solution Exclusivity Letter Decision, “[t]his express description of the circumstances in which exclusivity will not be forfeited for failure to obtain tentative approval makes it clear that, under other circumstances in which an applicant has failed to obtain tentative approval, regardless of what party might be responsible for that failure, the first applicant will forfeit exclusivity” (emphasis added). In other words, if OGD fails to take an approval action by the 30-month date described in FDC Act § 505(j)(5)(D)(i)(IV) because, for example, of other priorities that require the Office to shift its scarce resources, or simply because the 30-month date was not on the Office’s radar, 180-day exclusivity eligibility is forfeited.

As we previously reported (here, here, and here), there have been myriad cases in which FDA has already applied FDC Act § 505(j)(5)(D)(i)(IV) and determined that 180-day exclusivity was forfeited (or that the savings clause applied). A quick look at FDA’s Paragraph IV Certification List and FDA’s drug approval database shows that there are cases for post-MMA applications in which FDA did not make an approval decision within 30 months of ANDA submission; however, until FDA makes a final approval decision in those cases it will not be clear if 180-day exclusivity was actually forfeited. Nevertheless, the possibility of a forfeiture based on a failure on FDA’s part to meet the 30-month approval timeframe is certainly a possibility.

One upcoming case that could serve as a test case for FDA’s interpretation of FDC Act § 505(j)(5)(D)(i)(IV) is generic OPANA ER (oxymorphone HCl) Extended-release Tablets, 5 mg, 10 mg, 20 mg, and 40 mg. According to FDA’s Paragraph IV Certification List, the first ANDA containing a Paragraph IV certification was submitted to the Agency on November 23, 2007. Thirty months after that date is May 23, 2010. IMPAX Laboratories, Inc. (“IMPAX”) is believed to be a “first applicant” eligible for 180-day exclusivity. According to statements made during a recent earnings conference call, IMPAX is “pretty confident” that FDA will grant tentative ANDA approval by May 23rd; however, IMPAX President & CEO Larry Hsu commented during the call that “we do look at the plan B just in case. If we do not get the approval, we have some actions there that we have to take.” Among those actions under plan B consideration is presumably a lawsuit against FDA.

If FDA meets the May 23rd date for generic OPANA ER, then forfeiture under FDC Act § 505(j)(5)(D)(i)(IV) is moot and a lawsuit will have to wait for another day. But the broader generic drug industry concern with FDA’s implementation of FDC Act § 505(j)(5)(D)(i)(IV) remains. In 2003, when the MMA was enacted and the median ANDA approval time was around 17 months, a 30-month approval time probably seemed reasonable. It does not appear to be as reasonable today. Perhaps 30 months will appear reasonable once again in a future world where there are generic drug user fees that allow OGD to significantly decrease median ANDA approval times. Until that time, however, companies will have to work with OGD to ensure timely approval actions, or consider plan B options, such as litigation or pressing Congress for a legislative solution.